Tissue cultures of macrophages and naturally occurring animal mutants are used for these studies. Study of physiologic and biochemical parameters of these models is aimed at defining the milieu in which enzyme or gene replacement will be studied. Macrophages derived from circulating monocytes will survive in culture for approximately two weeks. Under special conditions, dividing cultures have been established without the use of transforming virus. These cells have survived more than six months. Alterations of lysosomal enzymatic activities have been recorded in both short and long term cultures. Estimation of lectin occurrence and function in these cells has been evaluated. The ability of cells to incorporate added lipids has been measured. Catabolism of added lipid has been compared in control and disease cells. Studies in a cat model of GM1 gangliosidosis have revealed that human placental Beta-galactosidase can be delivered to brain following blood-brain barrier opening. Study of animal models for the evaluation of enzyme and gene replacement is progressing.